Ultrasensitive olfactory system fabrication with doped aerogels

ABSTRACT

An array of sensor elements is formed by the incorporation of sensing materials into porous structures, creating sensing systems with extremely large surface areas with sensing molecules attached to mimic the large number of cilia of an olfactory system. In each sensor element, the sensing material or molecules are attached to spacer molecules or groups, which are attached to linker molecules or groups, which are attached to the porous substrate material. More specifically, a porphyrin doped aerogel material is used. The porphyrin sensing material is attached to the aerogel throughout its high surface area pore space. The porphyrin is covalently bonded to the silica network of the aerogel with a triethoxysilyl group linker that covalently attaches to the aerogel, and an alkyl group spacer.

RELATED APPLICATIONS

This application claims priority from provisional application 60/628,698filed Nov. 16, 2004.

BACKGROUND OF THE INVENTION

This invention relates generally to ultrasensitive sensors, includingsensors that may be used individually or that may be used in an array inartificial olfactory systems, and more particularly to the attachment ofsensing materials to substrates, most particularly porphyrin sensingmaterials to aerogel substrates, in ultrasensitive sensors.

The human olfactory system has about 100 million olfactory cells andeach cell has about 10 cilia resulting in about 1 billion sensingelements. The olfactory system of canines has orders of magnitude moresensing elements. It is this enormous number of sensing elements thatgives the ultrasensitivity to biological olfactory systems. While thenumber of olfactory sensors is very large, the number of differentolfactory sensors is much smaller, about 1000 in a human. Identificationof an odor is through pattern recognition and neural processing.

Artificial olfactory systems attempt to model the biological olfactorysystem. Arrays of nonspecific chemical sensors are used with signalprocessing to identify odorants through pattern recognition. Artificialolfactory systems are presently limited by the sensitivity of thesensors and the processing techniques.

U.S. Pat. No. 6,598,459 to Chi Yung Fu describes an approach to anultrasensitive sensor element and array for an artificial olfactorysystem. Ultrasensitivity is obtained by producing a very large surfacearea on the sensor to mimic the very large number of sensing elements inthe biological system. Also sophisticated fuzzy logic and neural networkprocessing are used to identify the detected patterns. The sensor isformed with a substrate of a very high surface area material (a “surfacearea increasing material”) on a conventional sensor body, typically anacoustic device or resonator such as a quartz crystal microbalance(QCM), a surface acoustic wave device (SAW), or a micromachinedresonator. The high surface area material is preferably an aerogel (orxerogel), but may also include nanotubes, porous carbons, ormicromachined materials. The high surface area material is coated withan odorant attracting or detecting material (sensing material),typically a polymer, to which the target molecules attach.

One particular combination of interest is porphyrin coated aerogel.There are a number of known techniques to deposit porphyrins ontosubstrates, including casting, Langmuir-Blodgett (LB) techniques, andself-assembly deposition. The casting method dissolves an appropriateporphyrin into chloroform and then applies the solution onto thesubstrate. Once the chloroform evaporates, a thin film of porphyrin willbe left behind on the surface of the substrate. However, there isconcern for repeatability and uniformity using such an approach todeposit porphyrins into porous structures such as aerogel. The LBtechniques are only good for deposition on another layer and not goodfor filling the pores of a structure. Self-assembly seems appropriatebut there are concerns regarding the penetration of the porphyrin intothe porous structure of aerogel and furthermore the manufacturing costand complexity will be high.

Thus it is important to obtain sensors in which the sensing material isstrongly attached to the porous substrate material. Otherwise thebenefit of the high surface area of the substrate will be lost.

SUMMARY OF THE INVENTION

The invention is an array of sensor elements that are formed by theincorporation of sensing materials into porous structures, creatingsensing systems with extremely large surface areas with sensingmolecules attached to mimic the large number of cilia of an olfactorysystem. In each sensor element, the sensing material or molecules areattached to spacer molecules or groups, which are attached to linkermolecules or groups, which are attached to the porous substratematerial. This arrangement provides for strong attachment of the sensingmaterial to the substrate. The invention also allows the creation ofultrasensitive single sensors.

The porous structure with sensing material forms a part of aconventional sensor, e.g. QCM, SAW device, resonator, or optical sensor.An array of such sensors combined with a measurement device and a signalprocessor form an artificial olfactory system. In an artificialolfactory system, each sensor is made of a different sensing material,but the different sensing materials are typically related, i.e. they aredifferent species from a single family, e.g. porphyrins. The differentsensing materials are nonspecific and together provide a signature thatidentifies target species. But the linkers and spacers in all thesensors of the array are the same, which greatly facilitatesfabrication.

More specifically, a porphyrin doped aerogel material is used. Theaerogel provides the high surface area porous structure. The porphyrinis the sensing material and is attached to the aerogel throughout itshigh surface area pore space. The porphyrin doped aerogel is made usingthe solution sol-gel process. The intact porphyrin is covalently bondedto the silica network of the aerogel through a spacer with a linker orbridge. More specifically, the linker or bridge is a terminaltriethoxysilyl group that covalently attaches to the aerogel, and thespacer is an alkyl group.

BRIEF DESCRIPTION OF THE DRAWINGS

In the accompanying drawings:

FIG. 1 illustrates the attachment of a sensing molecule in the pore ofan aerogel substrate through a bridge or linker molecule and a spacermolecule.

FIG. 2A is a cross sectional view of a sensor having a layer of aerogel,with a polymer coating, on top of a piezoelectric crystal.

FIG. 2B shows a magnified area of the aerogel/polymer layer of FIG. 2A.

FIG. 3 shows a complete artificial olfactory system with two sensingunits, a measurement unit, and a neural network or intelligentprocessing system.

DETAILED DESCRIPTION OF THE INVENTION

The basic principles of an ultrasensitive sensor element and array aredescribed in U.S. Pat. No. 6,598,459, which is herein incorporated byreference. However the type of sensor is not limited to the types ofsensors shown therein, but more broadly applies to any other type ofsensor where a high surface area may provide a higher amount of sensingmaterial, e.g. optical sensors.

In this invention, materials such as aerogel, xerogel, nanotubes, porouscarbon, zeolites, man-made structures such as those created bymicromachining or nanotube-like or dendrite-like growth processes, andany other materials that can provide large surface areas relative to thephysical dimensions of the sensor, are used as a substrate for thesensing system. Two appropriate molecules, A and B, are chosen to linkthe sensing molecule, S, to the substrate, Su. While the followingdescription is in terms of single molecules, there are of course manysimilar molecules attached through many spacer-linkers to each sensor toprovide the high sensitivity.

Molecule A has the attribute of having one side chain that can easilyattach to the surface of the substrate. Another end of molecule A hasthe property to attach easily to the B molecule. Molecule A is called alinker or bridge. Molecule B has the attribute of having a side chainthat can attach to molecule A, whereas another end can attach to thesensing molecule. Molecule B also has two additional attributes. It actsas a space extender so that the attached sensing molecule S would asmuch as possible be located in the center of the voids or pores of theporous substrate. Secondly, molecule B also acts as a “spring” or aspacer to release stress and tension to make the sensing system morereliable. Molecule B is called a spacer.

The sensing molecules can be chemically based for chemical detection aswell as biologically based for biological sensing. Examples of sensingmolecules can be different types of porphyrin molecules or differenttypes of amino acids. The members within these two families of moleculesare structurally similar but have diverse chemical and biologicallydifferent properties obtained simply by changing one or a few atomswithin the molecular structure. The similarity of the structures withinthe same family means that once an appropriate molecule B is found, thenmolecule B can be the spacer molecule for every member of the samefamily, and thus it can attach to the same A molecule to link to thesubstrate. This allows very efficient development of a sensor array suchas an olfactory system. There may be circumstances that molecule A andmolecule B can be collapsed into one single molecule. In other words, itacts as both the linker and the spacer, i.e. one end attaches directlyto S and another end attaches directly to Su while providing bothfunctions of the linker and the spacer.

Another aspect of this invention is that molecules A, B, and S can be“pre-fabricated together” in a chemical synthesis house and these“macromolecules” will be incorporated into the porous structures as inthe case of doping in semiconductor. This doping process allows adivide-and-conquer approach that makes implementing differentultra-sensitive sensors relatively simple and cost effective. Such anapproach represents essentially a single-step process and thus iselegantly simple. Doping in semiconductors has been done routinely inintegrated circuit processing and is a highly manufacturable process.

The above invention can be used for implementing a sensing system usingdifferent porphyrin molecules into xerogel/aerogel structures to form asensing array. The sensing array utilizes known types of sensors buttheir sensitivity is greatly enhanced by the high surface area withattached sensing material. The sensor array can be used, withappropriate signal processing, e.g. fuzzy logic and neural networks, inan artificial olfactory system or electronic nose. A single highsensitivity sensor may also be used by itself for various applications.

FIG. 1 schematically shows a Mn(III) porphyrin molecule attached to afunctionalized alkoxide linker —Si(OEt)₃ (triethoxysylil) through aspacer. The linker attaches to the aerogel substrate. The linkage formsa bridge between the porphyrin molecule and the aerogel matrix. By usingthe same linker, from the perspective of the aerogel/xerogel, it doesnot matter what porphyrin is attached. In other words, once successfullydeveloped for one porphyrin, the technology is essentially applicable toall other porphyrins. This drastically reduces the time of developmentof the sensor array. FIG. 1 also shows an alkyl spacer between theporphyrin molecule and the linker. The spacer decreases the mechanicaltensions during the drying process and thus would increase yield andreliability.

The viability of such an approach to prepare such doped aerogels hasalready been shown in the field of catalysis. M. Bonnett et al., “A NewMesoporous Hybrid Material: Porphyrin-Doped Aerogel as a Catalyst forthe Epoxidation of Olefins,” Adv. Funct. Mater. 2002, 12, No. 1,January, 39-42, shows the synthesis of Mn(III) porphyrin and porphyrindoped aerogel. L. Schmid et al., “A mesoporous ruthenium silica hybridaerogel with outstanding catalytic properties in the synthesis ofN,N-diethylformamide from CO2, H2 and diethylamine,” Chem. Commun.,1999, 2302-2304, shows a ruthenium phosphine complex functionalized bysilyl ether groups immobilized within a silica matrix to form dopedaerogel or xerogel. Similar fabrication techniques have also been usedto prepare optical materials for second harmonic generation experiments.J. P. Boilot et al., “Covalent Grafting of Optically Active molecules onSilica Gels,” shows the grafting of active organic molecules onto axerogel silica matrix using functionalized alkoxides with an alkylspacer to limit the degrees of freedom of the molecules. These papersare herein incorporated by reference. Thus the present invention usessimilar materials produced in other fields for a totally new use, tomake ultrasensitive sensors.

As shown in FIG. 2A, a sensor element 40 is formed from a piezoelectric(PZ) crystal oscillator 42 having an aerogel/polymer layer 44 on asurface 46. A pair of electrodes 47, 48 on opposed surfaces of PZcrystal 42 are used to apply a voltage across the crystal to induceoscillation. Layer 44 provides a high surface area and the ability tocapture odorant molecules. A region 50 is shown in greater detail inFIG. 2B. Aerogel substrate 52 has a thin coating of detection polymer 54thereon. Odorant molecules 56 penetrate the void spaces 58 in theaerogel substrate 52. Changes in the resonant frequency of oscillator 42produced by different odorant molecules are detected. The doped aerogelof the present invention, as illustrated in FIG. 1, is used to form thelayer 44. Crystal 42 is generally representative of any type of sensoron which layer 44 could be effective, e.g. an optical sensor such as awaveguide.

As shown in FIG. 3, artificial olfactory system 60 has a pair of sensorunits 62, each of which contains a plurality (e.g. 6) of sensor elements64. The outputs of the sensor elements 64 are measured by measurementdevice 66. Device 66 is a frequency measurement unit, e.g. a quartzcrystal microbalance, to detect frequency or mass change. Measurementdevice 66 produces a signature 68 which is input into an intelligentsignal processor 70, e.g. a neural network, that performs patternrecognition to detect, recognize and identify the odor molecules. Theindividual sensor elements 64 are nonspecific, i.e. they all respond toeach target molecule, producing a signature for that target, butdifferent signatures for different targets. Thus the individual sensorscan be made with different materials from a particular family, e.g.porphyrins, and the invention provides a single way to attach all thedifferent sensing materials.

Changes and modifications in the specifically described embodiments canbe carried out without departing from the scope of the invention whichis intended to be limited only by the scope of the appended claims.

1. A sensor array for an artificial olfactory system for detectingvarious targets, comprising: a plurality of sensor elements, each sensorelement comprising: a sensor body; a high surface area substrate on thesensor body and having a porous structure, the surface area of thesubstrate being substantially greater than the physical dimensions ofthe sensor body; linker molecules attached to the substrate throughoutits porous structure; spacer molecules attached to the linker molecules;sensing molecules attached to the spacer molecules throughout the porousstructure of the substrate; each sensor element being non-specific tothe targets and responding non-specifically to many different targets,the array of sensor elements producing signatures for various targets;wherein all sensor elements are formed of the same substrate, linkermolecules and spacer molecules, and each sensor element is formed of adifferent sensing molecule selected from a related family of sensingmolecules; wherein the substrate is an aerogel or xerogel, the sensingmolecule is a porphyrin, the linker molecule is a triethoxysylil, andthe spacer molecule is an alkyl.
 2. An artificial olfactory system fordetecting various targets, comprising: a sensor array comprising aplurality of sensor elements, each sensor element comprising: a sensorbody; a high surface area substrate on the sensor body and having aporous structure, the surface area of the substrate being substantiallygreater than the physical dimensions of the sensor body; linkermolecules attached to the substrate throughout its porous structure;spacer molecules attached to the linker molecules; sensing moleculesattached to the spacer molecules throughout the porous structure of thesubstrate; each sensor element being non-specific to the targets andresponding non-specifically to many different targets, the array ofsensor elements producing signatures for various targets; wherein allsensor elements are formed of the same substrate, linker molecules andspacer molecules, and each sensor element is formed of a differentsensing molecule selected from a related family of sensing molecules; ameasurement device connected to the sensor array to measure the outputsof the sensor elements of the sensor array; a pattern recognizingintelligent signal processor connected to the measurement device andtrained to detect a target by pattern recognition of the compositeresponses of all the sensor elements of the sensor array; wherein thesubstrate is selected from aerogel, xerogel, nanotubes, porous carbon,zeolites, or structures created by micromachining or nanotube- ordendrite-growth processes.
 3. The artificial olfactory system of claim 2wherein the sensor bodies are piezoelectric crystal oscillators, themeasurement device is a frequency measuring device for measuring changesin resonant frequency of the crystal oscillators caused by changes inmass of the sensor body substrates from binding of target molecules tosensing molecules, and the signal processor is a neural network.
 4. Theartificial olfactory system of claim 2 wherein the sensing molecules area porphyrin or an amino acid.
 5. The artificial olfactory system ofclaim 2 wherein the linker molecule is a triethoxysylil, and the spacermolecule is an alkyl.
 6. A method of forming a sensor array for anartificial olfactory system for detecting various targets, comprising:forming a plurality of sensor elements, each sensor element comprising asensor body, a high surface area substrate on the sensor body and havinga porous structure, the surface area of the substrate beingsubstantially greater than the physical dimensions of the sensor body,linker molecules attached to the substrate throughout its porousstructure, spacer molecules attached to the linker molecules, andsensing molecules attached to the spacer molecules throughout the porousstructure of the substrate, each sensor element being non-specific tothe targets and responding non-specifically to many different targets,the array of sensor elements producing signatures for various targets;wherein all sensor elements are formed of the same substrate, linkermolecules and spacer molecules, and each sensor element is formed of adifferent sensing molecule selected from a related family of sensingmolecules; wherein the substrate is an aerogel or xerogel, the sensingmolecule is a porphyrin, the linker molecule is a triethoxysylil, andthe spacer molecule is an alkyl.
 7. The method of claim 6 wherein thelinker, spacer, and sensing molecules are prefabricated intolinker-spacer-sensing macromolecules and the macromolecules areincorporated into the porous structure of each substrate by a dopingprocess.
 8. The artificial olfactory system of claim 2 wherein thesensing molecule is a porphyrin.
 9. The artificial olfactory system ofclaim 2 wherein the sensing molecule is an amino acid.
 10. Theartificial olfactory system of claim 2 wherein the linker molecule is atriethoxysylil.
 11. The artificial olfactory system of claim 2 whereinthe spacer molecule is an alkyl.
 12. The artificial olfactory system ofclaim 2 wherein the substrate is an aerogel or xerogel, the sensingmolecule is a porphyrin, the linker molecule is a triethoxysylil, andthe spacer molecule is an alkyl.
 13. The sensor array of claim 1 whereinthe sensor bodies are piezoelectric crystal oscillators.